Magnetic Nanocomposites with Cell Membrane Cloak for Electrochemical Profiling of Cancer‐Related MiRNAs

Specific quantification of multiplex miRNAs associated with cancers like non-small-cell lung carcinoma (NSCLC) provides a promising approach to assist accurate clinical diagnosis. Herein, an electrochemical method is developed for the simultaneous analysis of two NSCLC-related miRNAs. 3D tetrahedral DNA (TDNA) is first immobilized on the electrode surface as the sensing interface. The DNA nanostructure is previously modified with nine thiol anchors to assist firm immobilization and long-term storage. Single-stranded DNA probes with complementary sequences of target miRNAs and independent electrochemical labels are modified on the surface of cell membrane cloaked magnetic nanoparticles. In the presence of targets, duplex-specific nuclease (DSN)-assisted cleavage cycles release free signal strands, which can be captured at the TDNA modified electrode via reversible triplex formations. This design not only facilitates convenient reporting of miRNA-specific electrochemical signals but also makes the electrode regenerative for additional tests. The cost is significantly reduced, and ultrahigh sensitivity is achieved. This approach is successfully applied for the analysis of NSCLC samples (early and late stages), which opens a new avenue for non-invasive clinical applications with multiplex electrochemical detection.